New drug for Hemophilia A found in mice

One in 5000 males face the fact that they have Hemophilia A [1]. As an inherited disease carried on the X chromosome, it can at least be found early in a those affected. This disease causes someone to either not produce, or not produce a normal amount of a Factor VIII protein that is essential in the process of blood clotting. This abnormal protein or scarce protein is coded for by a mutated DNA sequence in the Factor VIII gene. Depending on what kind of mutation causes each individual's disease, the symptoms can range from mild to severe Hemophilia A. Life is not easy for those affected, especially those struggling with severe Hemophilia A. However regardless of severity, excessive bleeding will be a day to day struggle, and every day the hope is for a cure. Currently the only affordable treatment that is widely-used is concentrates. Doctors simply take healthy, normal proteins that someone with Hemophilia A is lacking and they transfer them into a patient's bloodstream when a wound occurs. A large percentage of people's bodies recognize these essential proteins as "foreign invaders", which leads to its creation of fighting agents (antibodies) to attack the "foreign" protein [2]. The immune system is known to protect our bodies from things it thinks are dangerous, even if it is wrong sometimes. As a result, the concentrates eventually fail to work in many people. Many of those affected by this need the concentrates the most; the severe cases. Scientists are now searching for an affordable alternative to the concentrates, but have not turned up much hope. Alternative concentrates have been made, only to eventually be rejected by their immune systems again. However, a recent study has found that using a different form of another factor necessary to completing the blood clotting process (Factor IX protein), it could fill the role that normally Factor VIII and Factor IX proteins are needed in combination to fulfill the blood clotting process (Figure 1). The scientists first silenced the function of the Hemophilia A factor in mice (stopping its function), and the different Factor IX proteins (which were hoped to rescue closer-to-normal blood clotting) were transferred into the mice. The results: shortened clotting times, reduced blood loss after a tail-clip, and regained blood clot formation. Even more promising news, is that the mice used in the experiments did not develop an immune response to this different form of Factor IX proteins! [3] The next step for this treatment is approval from the Food and Drug Administration in order to begin phase I clinical studies.

Figure 1. The Blood Clotting Cascade.
Observe how IXa (activated IX) requires VIIIa (activated VIII) to continue to the next step of the pathway.